The activation of carcinogens and anticancer agents to their cytoactive metabolites is catalyzed by a cytochrome P-450-dependent drug metabolism system in human and rat colon and colon tumors. The activities of the drug metabolism system are affected by gastrointestinal hormones. The goals of this proposal are to define the roles and mechanism of the gastrointestinal hormones on the regulation of the colonic drug metabolism system and to define the effects of the gastrointestinal hormones on colon and colonic tumor growth. Pursuit of these goals will involve identification of the forms of cytochrome P-450 present in colon and colon tumors and specification of the mechanisms regulating both the amount and functionality of the forms. We propose to purify and characterize colonic cytochromes P-450 to address these goals. We will also use techniques not requiring purification, such as definition of forms present in microsomes by antibody analysis and quantitation. We will also determine the effects of gastrointestinal hormones on cytochrome P-450 composition, development, growth rate and response to chemotherapeutic agents of colon tumor cells, In this way we will define the role of gastrointestinal hormones and the drug metabolism system of colon and colon tumors in carcinogenesis and in chemotherapy.